Some of the more ubiquitous and toxic contaminants of the nation's drinking water supplies are polychlorinated methanes, ethanes, and ethylenes. Most of these are formed during the chlorination process employed for water purification. Testing has shown that many of these compounds are carcinogenic when converted in vivo by microsomal enzymes to reactive metabolites. Several different biotransformation reactions appear to be involved, including oxidative and reductive dechlorination, dehydrohalogenation and nucleophilic substitution. Although these metabolic transformations should be well understood because of the implications to human health, very little definitive work has been done on this problem. An objective of the proposed research is to study the microsomal oxidative dechlorination of polychloroethanes. This class of compounds was chosen because it is the least well studied of the group. Metabolic products formed in vitro will be identified using gas chromatography/mass spectrometry and effects of induction, inhibition, age, sex, and genetics on metabolite formation will be measured. This data, together with that obtained using deuterium labeled substrates, will help to elucidate the reaction mechanisms involved. Another objective of the proposed research is to extend the usefulness of a recently developed in vitro screening test for environmental substances which impair the energy metabolism of human neutrophils and platelets. A microsomal metabolizing system will be added so that the cells are exposed to chemicals and their biotransformation products. This approach more closely mimics the invivo situation and has proven successful in other toxicity screening tests.